Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease.

ABSTRACT: Huntington's disease (HD) is a fatal, progressive neurodegenerative disorder. Prior studies revealed an increase in extracellular glutamate levels after evoking astrocytic SNARE-dependent exocytosis from cultured primary astrocytes from mutant huntingtin (mHTT)-expressing BACHD mice compared to control astrocytes, suggesting alterations in astrocytic SNARE-dependent exocytosis in HD. We used BACHD and dominant-negative (dn)SNARE mice to decrease SNARE-dependent exocytosis from astrocytes to determine whether reducing SNARE-dependent exocytosis from astrocytes could rescue neuropathological changes in vivo. We observed significant protection against striatal atrophy and no significant rescue of cortical atrophy in BACHD/dnSNARE mice compared to BACHD mice. Amino acid transporters are import

SUBMITTER: King AC 

PROVIDER: S-EPMC11583919 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature